The present studies evaluate rheological properties and in-vitro permeability properties of Escitalopram Oxalate (ECO) containing hydroxypropyl cellulose (Klucel HF, HPC) gels prepared with different carbon chain length containing fatty acids. The formulations were prepared by mixing solvent, escitalopram oxalate and kulcel HF (HPC) in homogenizer at 25000 RPM. A controlled stress rheometer was used to study the effect of different number of carbon chain fatty acids on the rheological properties and microstructure of HPC gels. The in-vitro permeability study was performed using human cadaver skin in order to evaluate the enhancing effect of fatty acids. The studies demonstrated that as the carbon chain length increased (C10-C18) the zero-shear viscosity, and yield stress value increased, which suggested that the stability of gel structure was increased with increase in carbon chain of fatty acids. Cohesive Energy was also depended on the carbon chain of fatty acids. There was decreased in cohesive energy as decrease in carbon chain of fatty acids. Temperature loop was created using heating and cooling temperature cycle. Oleic acid (C18) gave the best thermal stability with lowest temperature loop area. Increase in carbon chain length of fatty acids decreased the permeability enhancing effect of Escitalopram Oxalate through human cadaver skin during In-vitro permeability studies. The permeability of ECO through human cadaver skin was found to be in increasing order as capric acid> lauirc acid> Oleic acid> No-enhancer. Rheological studies could be useful to investigate the internal structure of HPC gels. Fatty acids alter the rheological properties of HPC gels such as zero shear viscosity, yield stress and cohesive energy. Moreover, In-vitro permeability results demonstrated that HPC gels containing fatty acids could be potential delivery system for transdermal delivery of ECO.